APPLICANT'S ABSTRACT: This application for a Mentored-Patient Oriented Research Career Development Award is designed to provide the candidate with skills and expertise in the use of functional neuroimaging in the area of alcoholism. The proposed research project integrates the candidate's skills in the clinical treatment of alcoholism with a training plan designed to develop skills in neuroimaging. Functional neuroimaging is a powerful tool to investigate brain activity. One area of alcoholism that has been relatively understudied by this new technology is the syndrome of alcohol withdrawal (AW). Alcoholism is characterized by neuronal adaptation to chronic alcohol use. Upon cessation of heavy alcohol use, alcohol dependent patients display an AW syndrome that likely reflects this neuroadaption. While acute AW symptoms are only manifest for 2-5 days, it is likely that readaption of the neuronal change takes much longer. There is a paucity of research that has systematically studied regional brain activity in humans during AW. Previous functional imaging studies have indicated that there is a global reduction in brain activity in AW. However, there is increased activity in the temporal lobes. The proposed project is focused on this area of investigation. Specifically, brain "activity" will be examined using a form of functional neuroimaging, known as SPECT imaging. In addition, both resting and drug (procaine)-stimulated activity states will be examined. The limbic system, a component of the temporal lobes, has been implicated as a significant brain component mediating AW. Accordingly, the limbic system, in general, and the amygdala in particular, will be the neuroanatomical targets of interest to this study. The proposed studies will extend and enhance prior work by attending to possible confounding issues ignored in other studies. In addition, the proposed studies will utilize state-of-the-art methodology and a novel methodological approach (pharmacological probe) to investigate brain activity in AW. Establishing the neuronal regions involved in the AW period may aid in understanding the neurobiology of AW. If specific abnormalities are documented, they may prove to be fruitful targets for pharmacological interventions in potentially preventing relapse to alcohol use. Finally, the utilization of the challenge paradigm proposed in these studies to unmask brain alterations and/or to exacerbate brain activity alterations that exist in the resting state could be a valuable model to help in the evaluation of new pharmacological intervention.